Objectives: Establish the safety and the maximum tolerated dose (MTD) of orally administered PCI-32765 in patients with recurrent B cell lymphoma. Determine pharmacokinetics (PK) of orally administered PCI-32765 Measure pharmacodynamic parameters to include drug occupancy of Btk, the target enzyme, and effect on biological markers of B cell function Samples for pharmacokinetics and pharmacodynamics will be collected as outlined in the protocol and shipped to Pharmacyclics, Inc. as specified below. Tissue samples will not be sent to Pharmacyclics, Inc. Rather, tissue samples will be obtained as outlined below. Biopsy specimens will be required from all patients before initiation of PCI-32765 treatment (pre-treatment biopsies). It is anticipated that roughly half of the patients will have accessible tumor tissue and will be rebiopsied prior to PCI-32765. These patients will also be biopsied 48 hours after the initial PCI-32765 dose. For the other patients, formalin fixed and paraffin embedded (FFPE) samples from previous biopsies will be analyzed. Gene expression profiling using Affymetrix U133plus2.0 arrays will be performed for all cases. For those cases with available fresh frozen pre-treatment biopsy samples, geneexpression profiling will be performed as described by the Staudt laboratory, with assignment to ABC or GCB subgroups based on a Bayesian predictor (Wright et al. PNAS 2003, 100:9991). On these patients, we will also obtain biopsy samples 48 hours post-treatment and profile gene expression similarly. Comparison with the pre-treatment sample will allow us to assess the ability of PCI-32765 to inhibit btk. For patients with only an FFPE biopsy sample, we will use a newly described method that can use RNA from FFPE biopsies to accurately predict ABC vs. GCB DLBCL subtypes (Williams et al. J Mol Diag 2010, in press). Briefly, RNA is extracted from FFPE samples with a Qiagen FFPE extraction kit followed by amplification using a kit from Nugen, prior to standard Affymetrix U133Plus2.0 array analysis. We will also perform where possible analyses of tumor mutations which include but are not be restricted to CARD11, ITAM and A20.